The blood-brain barrier is exactly what it says: a physical barrier between BLOOD and brain (or more specifically, between PLASMA and brain INTERSTITIAL FLUID). Its importance cannot be overstated: the bloodstream contains very many chemicals: some are required by the brain for effective functioning (such as GLUCOSE) and some act as information signals to the brain (such as HORMONES), but there are many chemicals that are not required by brain (and would be dangerous if present there) and of course DRUGS delivered into the bloodstream deliberately, either for therapeutic or recreational purposes, may or may not be wanted in brain. Those substances that need to be excluded are effectively barred by the blood-brain barrier; those that need access generally have to have that access regulated. (For example, the concentration of glucose in the blood fluctuates dramatically during the day. Brains need to be protected against surging levels of glucose, requiring instead a regulated and controlled flow.) Chemicals that cross the blood-brain barrier typically have a low MOLECULAR WEIGHT and high solubility in LIPIDS, or they cross by virtue of an active transport mechanism. In drug discovery research it is always important to know whether a compound can cross the blood-brain barrier: an agent intended to treat a neurological condition would normally be expected actually to enter brain tissue.
The existence of a barrier was noted first by Paul Ehrlich in the nineteenth century: he injected dye into the bloodstream and noted that it stained all tissues except the brain. The same dye injected into the cerebral VENTRICLES did stain brain tissue, indicating that something normally obstructed the passage of chemicals from blood to brain. The term blood-brain barrier was coined in 1900 by Lewandowski. The blood-brain barrier is formed by complex tight junctions between cells which physically prevent movement of fluids across the membranes.
There are a number of places where specialized barriers are formed: (1) the ENDOTHELIUM of blood vessels in brain form tight junctions to prevent fluid escaping from the bloodstream into the brain interstitial fluid. (2) The CHOROID PLEXUS is CONNECTIVE TISSUE found in the VENTRICLES of the brain. It is here that CEREBROSPINAL FLUID (CSF) is formed, this accumulating in the ventricles and flowing out into the extracellular spaces around the NEUROPIL of the brain. A barrier in the choroid plexus epithelium prevents direct exchange of fluids between blood and CSF. (3) The NEUROTHELIUM is a barrier formed in the ARACHNOID MEMBRANE: cells form a barrier on the outside of the arachnoid membrane to prevent blood from vessels in the DURA MATER escaping into brain. (4) There are specialized sites known as the CIRCUMVENTRICULAR ORGANS where exchange between brain and blood can take place. Such sites are critically involved in monitoring the composition of the blood-stream, but nevertheless possess a form of barrier that allows the required communication to take place while preventing non-selective influx of material into brain. This barrier is made of TANYCYTES, specialized ependymal cells.
All of these—blood vessel endothelium, choroid plexus endothelium, neurothelium, tanycytes—show formation of tight junctions to prevent unwanted movement of fluid. Clearly though, blood contains substances such as glucose that need to be extracted by the brain. Specialized transport mechanisms exist to take such substances from the bloodstream and divert them to the required brain sites. ASTROCYTES are involved in this process: they make contact with blood vessels and, using specialized transporter mechanisms, effect passage of required substances into brain in a controlled manner.
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